This invention relates to the use of differentiated cells in the treatment of neurodegenerative disorders.
Parkinson""s disease is a neurodegenerative disorder affecting an estimated one million patients in the United States. Several strategies are being pursued to develop new therapies for Parkinsonian patients. These techniques range from the use of dopaminotrophic factors (Takayama et al., (1995) Nature Med. 1, 53-58) and viral vectors (Choi-Lundberg et al., (1997) Science 275, 838-841) to the transplantation of primary xenogeneic tissue (Deacon et al., (1997) Nature Med. 3, 350-353). Fetal nigral transplantation is a clinically promising experimental treatment in late stage Parkinson""s disease. More than 200 patients have been transplanted worldwide and clinical improvement was confirmed (Olanow et al. (1996) Trends Neurosci. 19, 102-109 and Wenning et al., (1997) Ann.Neurol. 42, 95-107) and was correlated to good graft survival and innervation of the host striatum in post mortem studies of transplanted patients (Kordower et al., (1995) N.Engl.J.Med. 332, 1118-1124).
Cell transplantation usually involves transplanting primary cells or immortalized cells into a patient. There has been mixed success in clinical trials where primary cells have been utilized. It is believed that the inadequate supply of primary cells or use of different proportions of primary cell types cause many trials to fail or to give inconsistent results.
Furthermore, neural transplantation remains a controversial procedure. Current transplantation treatment involves the use of material derived from at least 3-5 embryos to obtain a clinically reliable improvement in the patient. This poses an enormous logistical and ethical dilemma.
For these reasons, much effort has been devoted to finding alternatives to fetal tissue for use in transplantation. Although use of neural stem cells is promising because stem cells can be proliferated prior to differentiation, such stem cells have a relatively low proportion (about 0.1%) dopaminergic neurons. Since the clinical efficacy of transplants is in large part dependent upon the number of dopaminergic cells transplanted, finding a method to increase the proportion of dopaminergic cells in a CNS stem cell culture would have obvious clinical benefits. Additionally, successful numerical expansion of primary CNS precursors could alleviate some of the ethical and technical difficulties involved in the use of human fetal tissue. There is thus a need for a process that will provide sufficient viable cells for a reliable, effective clinical cell transplantation.